The theoretical construct of resilience, better-than-expected outcome following potential risk, provides an innovative framework for the longitudinal study of intrauterine cocaine exposure (IUCE) & intrauterine substance exposure (IUSE). Resilience evolves from person/environment interactions, which may buffer the impact of biologic & social risks. We propose a masked multidisciplinary longitudinal follow-up of 140-150 urban primarily African American/African Caribbean participants aged 18-24 (50% with IUCE), continuously followed since birth to document risks, protective & promotive factors in multiple domains. Unique features of the already collected & proposed data set include: Ainsworth attachment classification at 12 months, repeated prospective measurement since infancy of the caregiver's & child's exposure to violence, repeated measures of material hardship, & parents' incarceration, with the addition in this cycle of measures of discrimination, positive ethnic identity, & quality of young adult intimate relationships 61% of the sample initiated substance use by age 16 by self-report or urine assay. During the proposed period of study (4/1/2010 - 3/31/2015) the participants enter the developmental epoch when the emergence of SUDs, possible recovery from such disorders, & ability to undertake early adult roles become measurable, & executive & memory functions mature. We focus on selected biological contextual factors, which may be crucial in determining resilience & risk in these domains. We consider as potential biologic factors among others: gender, birth weight, IUCE, age at assessment, & a novel composite measurement of overall level of intrauterine substance exposures (IUSE) including levels of cocaine, tobacco, alcohol, & marijuana in a single scale, as well as the individual substances as distinct variables. The participant's timing of initiation & concurrent level of adolescent / young adult use of psychoactive substances are both indicators of biologic risk to the still developing central nervous system & a major outcome. We will analyze the influence of potentially buffering contextual factors from infancy to young adulthood contributing to: 1) Freedom from SUDs; 2) Greater adaptive role function including fewer HIV risk behaviors, later childbearing, fewer psychiatric symptoms, less criminal behavior, & positive adaptation in education, employment & personal relationships; & 3) Expected maturation of executive & memory functions. We propose generalized mixed linear models to utilize fully the longitudinal nature of the data, including growth curve models to delineate trajectories, stratified & interaction models to examine moderators, & structural equation path models to evaluate mediation. IUSE impacts many Americans of all ethnic groups ranging from infants to adults. This sample represents a demographic, which, compared to other groups, suffers more adverse life consequences from substance use & which, with or without IUSE, faces disproportionate levels of community stressors. Identification of factors fostering resilience in this context of health disparities is of particular scientific &